Disease Review for FINAL

Question 1

Cystic Fibrosis

Answer 1

AR, CFTR mutation, modifier genes, Caucasian prevalence

Question 2

Sickle Cell Anemia

Answer 2

AR, heterozygote advantage, African prevalence

Question 3

Thalassemia

Answer 3

AR, heterozygote advantage, Mediterranean prevalence

Question 4

Xeroderma Pigmentosum

Answer 4

AR, DNA repair error

Question 5

Spinal Muscular Atrophy

Answer 5

AR, muscle wasting, “frog leg position”

Question 6

PKU

Answer 6

AR, pleiotrophy

Question 7

Tay Sachs

Answer 7

AR, Ashkenazi prevalence, “cherry red spot”

Question 8

Achondroplasia

Answer 8

AD, Paternal age effect, de novo mutations high

Question 9

Alzheimer Disease

Answer 9

AD, also multifactorial, HLA associations

Question 10

Hereditary Breast and Ovarian Cancer

Answer 10

AD, BRCA 1 and 2 gene mutations, DNA repair error, Founder effect (Ashkenazis)

Question 11

Familial Hypercholesterolemia

Answer 11

AD, LDL receptor mutation, cornea and tendon xanthomas

Question 12

Hereditary Nonpolyposis Colon Cancer

Answer 12

AD, Microsatellite instability, DNA repair error, germline and somatic mutations involved

Question 13

Holoprosencephaly

Answer 13

AD, SHH mutation

Question 14

Huntington Disease

Answer 14

AD, Tri-nucleotide repeats, anticipation

Question 15

Marfan Syndrome

Answer 15

AD, Dominant negative mutation, FBN1 gene (microfibrils, fibrillin-1), variable expressivity homocystinuria presents with similar phenotype (locus hetero), usually have ocular, skeletal and cardio system implications

Question 16

Retinoblastoma

Answer 16

AD, Tumor suppressor mutation, two-hit hypothesis, ↑ severity with inherited mutation than somatically gained mutations

Question 17

Neurofibromatosis

Answer 17

AD, “café au lait” spots, De novo mutations

Question 18

Familial Adenomatous Polyposis

Answer 18

AD, Risk of colon cancer

Question 19

Osteogenesis Imperfecta

Answer 19

AD, Type 1 collagen mutation, COL1A1 and COL1A2 genes, blue sclera, mostly dominant negative mutations

Question 20

Fragile X syndrome

Answer 20

X-linked, Trinucleotide repeats, anticipation

Question 21

Duchene Muscular Dystrophy

Answer 21

X-linked, Females with varying expressivity due to random X inactivation (skewing)

Question 22

Deafness

Answer 22

AR or AD, locus heterogeneity (2 deaf parents can have non deaf children that are compound heterozygotes)

Question 23

Trisomy 18

Answer 23

i. Congenital malformations
ii. Clenched hand
iii. Hypotonia
iv. High risk of wilms tumors

Question 24

Trisomy 13

Answer 24

i. Microcephaly, holoprosencephaly, microphtalmia

ii. Polydactyly

Question 25

Trisomy 21

Answer 25

i. Hypotonia ii. Single palmar crease* iii. CHD iv. Extra nuchal folds* v. Lots of Robersonian Translocations

Question 26

Cri du Chat

Answer 26

i. Deletion ii. Microcephaly iii. Weak, cat like cry iv. Karyotype or FISH

Question 27

Angelman

Answer 27

i. Microdeletion of maternal 15q ii. Genomic imprinting iii. Contiguous gene syndrome

Question 28

Prader Willi

Answer 28

i. Microdeletion of paternal 15q ii. Genomic imprinting iii. Contiguous gene syndrome

Question 29

Turner Syndrome

Answer 29

i. 45, X ii. NOT related to maternal age/caused by non-disjunction iii. Nuchal folds, webbed neck, widely spaced nipples iv. Coarctation of aorta

Question 30

Klinefelter

Answer 30

i. XXY | ii. Small testicles, tall stature, gynecomastia, learning disabilities

Question 31

XXY Male

Answer 31

i. Radial-ulnar synostosis

Question 32

Myoclonic Epilepsy w/ Red Ragged Fibers

Answer 32

i. Mitochondrial DNA inheritance | ii. Biopsy red ragged fibers

Question 33

Rett Syndrome

Answer 33

i. De novo mutation ii. Occurs mostly in girls iii. Microcephaly, scoliosis, learning disabilities

Question 34

CML

Answer 34

i. Chromosomal translocation results in oncogenesis | ii. Fused BCR-ABL protein

Question 35

Hurlers

Answer 35

AR, mucopolysacc disorder

Question 36

Myopia

Answer 36

most common ocular feature of Marfans, displacement of lens, 60% of affected individuals

Question 37

Dx of Marfans w/ and w/o Family Hx

Answer 37

w/ Hx - 1 system involved major, 1 system involved minor | w/o Hx - 2 systems involved major, 1 system involved minor

Question 38

Prevalence/recurrence of congenital malformations

Answer 38

2% newborns have congenital malformations that are multifactoral, recurrence risk is 1-5%

Question 39

Polygenic vs multifactorial trains

Answer 39

polygenic - multiple genes at different loci, excludes environmental effects multifact - takes environment and stochastic events into account with multi genes at different loci

Question 40

Liability and threshold

Answer 40

phenotype does not develop unless the individual crosses threshold through cumulative effects of genetic, environmental and stochastic components

Question 41

Multifactorial disease affecting 1st degree relatives

Answer 41

no more that 5-10%, cant be determined genetically, use empirical risk based on population

Question 42

Recurrence risk for multifactorial

Answer 42

1) decreased with more distantly related relatives 2) higher if more than one family member is affected 3) higher depending on severity of proband 4) if gender isnt equal, offspring of less frequently affected gender has higher recurrence

Question 43

Genocopy v phenocopy

Answer 43

genocopy is different genes make similar phenotypes, but arent the same (not locus hetero) phenocopy is environment makes similar phenotype to genetic mutation

Question 44

Restriction point

Answer 44

G1

Question 45

CDK (MPF)

Answer 45

arrests oocytes in G2 until hormonal stimulation triggers entry into M phase

Question 46

Cdc28/Cdc2

Answer 46

protein kinase

Question 47

What does MPF contain

Answer 47

cyclin B - regulatory subunit protein kinase cdc2 as catalytic subunit terms Cdk together

Question 48

Wee1 protein kinase

Answer 48

inhibitory P of tyr and thr near NH3 terminus of cyclin B-cdc2

Question 49

Cdc25 phosphatase

Answer 49

activating dephosphorylation of cyclin B-cdc2, which goes on to phos other things

Question 50

When does cyclin B synthesis start? What happens to it in the end?

Answer 50

S phase, degraded by action of cdc2 in ubiqi-med-protease

Question 51

Cip/Kip

Answer 51

tumor suppressor genes (p21, 27, 57), promiscuous binding, Cdk4/cycD, 6/D, 2/D, 2/A

Question 52

Ink4

Answer 52

tumor suppressor genes (p15, 16, 18, 19), more specific, Cdk4/D, 6/D

Question 53

G1 checkpoint

Answer 53

DNA damage, p53 makes p21 when DNA damage occurs, p21is cip/kip and inhibits many cdk/cyclin complexes (Cdk2/cyclinE), arrested in G1

Question 54

G2 checkpoint

Answer 54

DNA damage, Chk1 phosphorylates Cdc25, so doesnt dephos/activate Cdc2/cyclinB, arrested in G2

Question 55

TGFb

Answer 55

induced by CKI p15 (Ink4) binds Cdk4,6/D arrests cell in G1

Question 56

Cyclin D syn.

Answer 56

induced by Ras/Raf/ERK, cyclin D phosphorylates Rb, which removes it from binding EF2 so cell cycle can progress to transcription

Question 57

tumor suppressor genes

Answer 57

recessive, 2-hit model

Question 58

Retinoblastoma

Answer 58

del. of 13q, sporadic (AA) vs familial (Aa)

Question 59

Gate keepers

Answer 59

genes that directly control cellular growth/dif, Ex: p53, Rb, p16Ink4

Question 60

Caretakers

Answer 60

DNA repair, cell cycle checkpoints, Ex: BRCA1/2

Question 61

Li-Fraumeni syndrome

Answer 61

germline mutation in p53, develop cancer, onset of 30

Question 62

Tumor initiator vs promotor

Answer 62

initiator - chemical that alters structure of DNA | promoter - chemical doesnt alter structure, but promotes cell division

Question 63

Burkitt's lymphoma

Answer 63

balanced translocation of c-myc gene adjacent to Ig heavy chain, leads to over expression of c-myc

Question 64

Chronic myelogenous leukemia

Answer 64

translocation where bcr fused with abl, results in chimeric protein

Question 65

ret oncogene

Answer 65

one exception to oncogenes not be inherited, this gene is inherited

Question 66

Familial adenomatous polyposis

Answer 66

80% carry APC gene mutation in germline